Evolución tardía del Síndrome de Ebstein: presentación de caso clínico / Late evolution of Ebstein's Syndrome: clinical case presentation

Ebstein's anomaly is a rare congenital heart defect that affects the right ventricle. It can cause paradoxical embolism, cyanosis and arrhythmias due to atrialization and apical descent of the tricuspid orifice. Arrhythmias are common in adults, and biventricular failure is associated with less favorable outcomes. Diagnosis is based on clinical and electrocardiographic criteria and treatment requires a multidisciplinary approach. CLINIC CASE: A 77-year-old Chilean male patient with a history of type 2 diabetes mellitus, high blood pressure, dyslipidemia, and atrial fibrillation (AF). Subsequently, he developed dyspnea and severe hypertension, acute heart failure. Left ventricular hypertrophy, severe atrial dilation, mild to moderate valvular insufficiency and possible pulmonary hypertension were found by echocardiograms. These results were confirmed by an Echo-Doppler, which revealed atrialization of the right ventricle and septal dyskinesia. DISCUSSION: Patient with valvular insufficiencies and persistent AF, identified by Doppler ultrasound, is an example of how Ebstein's Anomaly can be diagnosed later. The value of echocardiography in diagnosis and how comorbidities such as hypertension and dyslipidemia can worsen the condition is highlighted in this case. In patients with RV widening or severe tricuspid regurgitation, even without symptoms, early surgical intervention is essential to improve survival and cardiac function.

La anomalía de Ebstein es un defecto cardíaco congénito poco común que afecta al ventrículo derecho. Puede causar embolia paradójica, cianosis y arritmias por atrialización y descenso apical del orificio tricúspide. Las arritmias son comunes en los adultos y la insuficiencia biventricular está relacionada con resultados menos favorables. El diagnóstico se basa en criterios clínicos y electrocardiográficos y el tratamiento requiere un enfoque multidisciplinario. CASO CLÍNICO: Paciente masculino de 77 años, chileno, con antecedentes de diabetes mellitus tipo 2, hipertensión arterial, dislipidemia y fibrilación auricular (FA). Posteriormente, presentó disnea e hipertensión grave, insuficiencia cardíaca aguda. Hipertrofia ventricular izquierda, dilatación auricular severa, insuficiencia valvular leve a moderada y posible hipertensión pulmonar fueron hallados por ecocardiogramas. Estos resultados fueron confirmados por un Eco-Doppler, que reveló la atrialización del ventrículo derecho y la diskinesia septal. DISCUSIÓN: Paciente con insuficiencias valvulares y FA persistente, identificada por Eco-Doppler, es un ejemplo de cómo la Anomalía de Ebstein puede ser diagnosticada más tarde. El valor de la ecocardiografía en el diagnóstico y cómo las comorbilidades, tales como la hipertensión y la dislipidemia, pueden empeorar la condición, lo cual se resalta en este caso. En pacientes con ensanchamiento del VD o regurgitación tricuspídea grave, aunque no presenten síntomas, es fundamental una intervención quirúrgica temprana para mejorar la supervivencia y la función cardíaca.

Tumores en ovario en pediatría / Ovarian tumors in pediatrics

Los tumores de ovario en la edad pediátrica son raros, representan 1-5 % de los tumores infantiles, con una incidencia anual de 2,6 casos por cada 100.000 pacientes. La mayoría son benignos y se tratan de quistes funcionales, sin embargo, entre 10-20 % son malignos y generalmente se presentan en adolescentes; estos últimos, se dividen en 3 grupos: tumores epiteliales, germinales, y estromales o de células sexuales. Método: Estudio retrospectivo de tipo transversal, observacional, no experimental. Se analizaron los pacientes con diagnóstico de tumor de ovario, ingresados en el Servicio de Cirugía Pediátrica del Hospital de Niños "Dr. José Manuel de los Ríos", entre el 1 de enero de 2017 y 01 de julio de 2022. Resultados: 18 pacientes incluidos en el estudio, con edad media de 8,23 años (DE 4,77); los síntomas más frecuentes presentados al momento del ingreso fueron: aumento de volumen abdominal (52,94 %, 9 pacientes), y dolor abdominal (35,29 %, 6 pacientes), entre otros. Reporte patológico: 2 pacientes con quistes de ovario funcional (11,76 %) y 16 pacientes con tumor neoplásico (88,23 %), de los cuales 8 fueron germinales (53,33 %), 5 tumores epiteliales (33,33 %) y 2 pacientes con linfoma (13,33 %). Conclusión: Los tumores de ovario en general tienen una edad promedio de presentación de 8 años y los tumores neoplásicos se presentaron principalmente en adolescentes, siendo el tipo histológico más frecuente el tumor germinal y dentro de este grupo el teratoma quístico maduro. (AU)

Ovarian tumors in pediatric age are rare, representing 1-5 % of childhood tumors, with an annual incidence of 2.6 cases per 100,000 patients. Most of them are benign and functional cysts; however, between 10-20 % are malignant and generally occur in teenagers; the latter are divided into 3 groups: epithelial, germinal, and stromal or sex cell tumors. Methods: Retrospective, cross-sectional, observational, non-experimental study. Patients with a diagnosis of ovarian tumor, admitted to the Pediatric Surgery Service of the Children's Hospital "Dr. José Manuel de los Ríos", between January 01, 2017 and July 01, 2022, were analyzed. Results: 18 patients included in the study, with mean age 8.23 years (SD 4.77); the most frequent symptoms presented at admission were: increased abdominal volume (52.94 %, 9 patients), and abdominal pain (35.29 %, 6 patients), among others. Pathological report: 2 patients with functional ovarian cysts (11.76 %) and 16 patients with neoplastic tumor (88.23 %), of which 8 were germinal (53.33 %), 5 epithelial tumors (33.33 %) and 2 patients with lymphoma (13.33 %). Conclusion: Ovarian tumors in general have an average age of presentation of 8 years and neoplastic tumors occurred mainly in teenagers, the most common histological type being the germ cell tumor and within this group the mature cystic teratoma. (AU)

Familial florid cemento-osseous dysplasia: an overview of a rare entity

Familial florid cemento-osseous dysplasia (FFCOD) is distinct from the sporadic variant and may often be confused with familial conditions presenting with lesions resembling cemento-ossifying fibromas. The current review aims to elucidate the FFCOD variant better and discuss distinguishing features with sporadic florid COD. A review of the literature on FFCOD cases using Google Scholar and PubMed was performed and summarised. A total of 11 articles with 36 patients were included in the current review. The clinical and radiologic presentations and the pertinent differences from the sporadic variant were discussed. The familial form shows advanced sclerosis and extensive distribution at a younger age, together with impacted teeth and bony expansion in the anterior mandible. Furthermore, distinguishing features from the most important differential diagnoses of other hereditary fibro-osseous conditions, including familial gigantiform cementoma (FGC), hyperparathyroidism jaw tumour syndrome (HP-JTS) and gnathodiaphyseal dysplasia (GDD) are discussed. (AU)

Síndrome de Robinow autosómico recesivo en una familia con dos hermanos afectados. Reporte de caso / Autosomal recessive Robinow syndrome in a family with two affected siblings: a case report

El síndrome de Robinow es una enfermedad rara, de origen genético causada por mutaciones en diversos genes de la vía de señalización Wnt, entre ellos: WNT5A, DVL1, DVL3, ROR2, NXN y FZ2. El síndrome se caracteriza por anomalías craneofaciales, malformaciones en extremidades y alteraciones genitourinarias. Se presentan dos hermanos nacidos de padres sanos con manifestaciones típicas del Síndrome de Robinow, el estudio de la genealogía sugiere un mecanismo de herencia autosómico recesivo. El síndrome de Robinow ha sido reportado en muy pocas ocasiones en la literatura científica internacional, por este motivo, reportes como el del presente artículo son un aporte importante al conocimiento de las características clínicas y el mecanismo de transmisión del síndrome. Nuestro artículo se constituye en el primer reporte boliviano del síndrome y uno de los pocos que reporta dos hermanos afectados.

Robinow syndrome is a rare genetic disorder caused by mutations in various genes within the Wnt signaling pathway, including WNT5A, DVL1, DVL3, ROR2, NXN, and FZ2. The syndrome is characterized by craniofacial anomalies, limb malformations, and genitourinary disorders. Two siblings born to healthy parents present typical manifestations of Robinow syndrome. Genealogical analysis suggests an autosomal recessive inheritance mechanism. Although Robinow syndrome has been rarely reported in the international scientific literature, articles like the present contribute significantly to understanding the clinical features and transmission mechanism of the syndrome. Our article represents the first Bolivian report on this syndrome and is one of the few that describes two affected siblings.

Ictiosis epidermolítica en un recién nacido: reporte de un caso / Epidermolytic ichthyosis in newborns: clinical case study / Ictiose epidermolítica em recém-nascido: relato de caso

La ictiosis epidermolítica es una genodermatosis de herencia autosómica dominante poco frecuente que requiere un diagnóstico oportuno, idealmente prenatal, para así brindar una asistencia neonatal adecuada, iniciar un tratamiento precoz y de esta manera disminuir su morbimortalidad. Se caracteriza por la formación de ampollas, múltiples erosiones y descamación con eritrodermia desde el nacimiento. Todos los tipos de ictiosis queratinopáticas son causadas por mutaciones en los genes de la familia de queratina KRT1, KRT2 y KRT10. Se presenta el caso clínico de un neonato de 9 días de vida, nacido en el interior del país, con diagnóstico de ictiosis epidermolítica y antecedente familiar de primer grado con la misma enfermedad. El interés de esta publicación radica en la descripción de una genodermatosis de baja frecuencia, reconocer la importancia del diagnóstico precoz, conocer el manejo, las complicaciones y destacar la importancia de la atención por un equipo multidisciplinario conformado por neonatólogo, dermatólogos, genetistas y pediatras.

Epidermolytic ichthyosis is a rare genodermatosis with autosomal dominant inheritance, which requires timely diagnosis, ideally prenatal diagnosis, in order to provide adequate neonatal care, start early treatment and thus reduce morbidity and mortality. It is characterized by the formation of blisters, multiple erosions and scaling with erythroderma from birth. All types of keratinopathic ichthyoses are caused by mutations in the genes of the keratin family KRT1, KRT2 and KRT10. We present the clinical case of a 9-day-old newborn from the interior of the country, with diagnosis and family history of epidermolytic ichthyosis. The interest of this publication lies in the description of a low-frequency genodermatosis, recognizing the importance of early diagnosis, understanding the management, complications and highlighting the importance of a multidisciplinary care team integrated by a neonatologist, dermatologists, geneticists and pediatricians.

A ictiose epidermolítica é uma genodermatose autossômica dominante rara que requer diagnóstico oportuno, idealmente pré-natal, para fornecer cuidados neonatais adequados, iniciar o tratamento precoce e, assim, reduzir sua morbidade e mortalidade. Caracteriza-se pela formação de bolhas, múltiplas erosões e descamação com eritrodermia desde o nascimento. Todos os tipos de ictioses queratinopáticas são causados por mutações nos genes da família da queratina KRT1, KRT2 e KRT10. É apresentado o caso clínico de um recém-nascido de 9 dias, nascido no interior do país, com diagnóstico de ictiose epidermolítica e história familiar de primeiro grau com a mesma doença. O interesse desta publicação reside na descrição de uma genodermatose de baixa frequência, reconhecendo a importância do diagnóstico precoce, conhecendo o manejo, as complicações e destacando a importância do atendimento por uma equipe multidisciplinar composta por neonatologistas, dermatologistas, geneticistas e pediatras.

Prática de cuidado às pessoas com doença de huntington na perspectiva de familiares cuidadores / Care practices for people with huntington's disease from the perspective of family caregivers / Prácticas asistenciales para personas con enfermedad de huntington desde la perspectiva de los cuidadores familiares

RESUMO Objetivo: conhecer as práticas do cuidado às pessoas com doença de Huntington. Método: estudo qualitativo, que utilizou o referencial do Cuidado Centrado no Paciente e na Família, realizado com 20 familiares cuidadores de pessoas com Huntington. A coleta de dados ocorreu mediante entrevista semiestruturada, nos meses de fevereiro e março de 2022, via Google Meet, e após transcritas na íntegra foram submetidas à Análise de Conteúdo. Resultados: a prática de cuidado às pessoas com Huntington necessita de adaptações no ambiente, de reajuste na rotina e improvisação de instrumentos de auxílio. A dificuldade para obtenção do diagnóstico gera a proatividade do familiar em busca de conhecimento para melhorar as condições de cuidado. Conclusão: embora trate-se de uma doença rara, as ações de cuidado referidas são semelhantes àquelas realizadas para pessoas com outras doenças crônicas. Contudo, o reconhecimento das práticas de cuidado realizadas pelos familiares pode oferecer subsídios para o planejamento da assistência pelos enfermeiros.

ABSTRACT Objective: to learn about care practices for people with Huntington's disease. Method: a qualitative study using the Patient- and Family-Centered Care framework, carried out with 20 family caregivers of people with Huntington's disease. Data was collected through semi-structured interviews, in February and March 2022, via Google Meet, and after being transcribed in full, it was submitted to Content Analysis. Results: The practice of caring for people with Huntington's requires adapting to the environment, readjusting the routine, and improvising aids. The difficulty in obtaining a diagnosis makes family members proactive in their search for knowledge to improve care conditions. Conclusion: although this is a rare disease, the care actions mentioned are like those carried out for people with other chronic diseases. However, recognizing the care practices carried out by family members can help nurses plan their care.

RESUMEN Objetivo: conocer las prácticas de atención a las personas con enfermedad de Huntington. Método: estudio cualitativo utilizando el marco de Atención Centrada en el Paciente y la Familia, realizado con 20 cuidadores familiares de personas con enfermedad de Huntington. Los datos se recogieron mediante entrevistas semiestructuradas, en febrero y marzo de 2022, a través de Google Meet, y tras ser transcritos en su totalidad, se sometieron a Análisis de Contenido. Resultados: la práctica de la atención a las personas con Huntington requiere adaptar el ambiente, reajustar la rutina e improvisar ayudas. La dificultad en obtener un diagnóstico genera proactividad por parte de los familiares en la búsqueda de conocimientos para mejorar las condiciones de atención. Conclusión: aunque se trate de una enfermedad rara, las acciones de cuidado mencionadas son similares a las que se llevan a cabo para personas con otras enfermedades crónicas. No obstante, reconocer las prácticas de atención que llevan a cabo los familiares puede ayudar a las enfermeras a planificar su asistencia.

An Atypical Cause of a Child Limp: A Gorham-Stout Disease with a Vanishing Hip / Uma causa atípica de claudicação infantil: Síndrome de Gorham-Stout com quadril fantasma

Abstract Gorham-Stout disease (GSD) is a rare bone disease characterized by an abnormal proliferation of endothelial-lined vessels and destruction of the affected bone. As it affects commonly children and young adults, it is associated with significant morbidity and mortality. To date, there is no established treatment strategy for GSD. We report through this observation a rare case of GSD in a child located in the hip and the iliac crest.

Resumo A síndrome de Gorham-Stout (SGS) é uma doença óssea rara caracterizada pela proliferação anormal de vasos endoteliais e destruição do osso acometido. Por ser comum em crianças e adultos jovens, causa morbidade e mortalidade significativas. Até o momento, não há estratégia terapêutica estabelecida para a SGS. Relatamos um caso raro de SGS no quadril e na crista ilíaca de uma criança.

Continuous Unilateral Cephalalgia Due to Systemic Lupus Erythematosus: A Case Report / Cefaleia unilateral contínua por lúpus eritematoso sistêmico: relato de caso

BACKGROUND: Hemicrania continua is a rare form of cephalalgia featuring a chronic and persistent headache in only one side of the head. OBJECTIVES: In this report, we present a case of a patient with hemicrania continua and systemic lupus erythematosus (SLE). METHODS: We collected patient data through the electronic medical record. Afterward, we reviewed the literature regarding hemicrania continua and its pathophysiology and correlation with neurovascular alterations, inflammation, and SLE. RESULTS: A 42-year-old woman visited the emergency department due to worsening constant unilateral cephalalgia that had been present for the past 6 months. The patient reported a highly intense (10/10) headache in the entire left hemicrania that radiated to the left shoulder. During physical examination, she presented with nystagmus, vertigo, and aggravated cephalalgia associated to body movement and, despite having no optic nerve thickening. In addition, she had jaundice, tachycardia, and splenomegaly. Complimentary exams found deep anemia, depletion in complement system and anti-nuclear factors, suggesting a possible hemolytic anemia (AIHA) due to SLE. Treatment was initiated with hydrocortisone and prednisone, associated with amitriptyline, fluoxetine and diazepam, reaching full remission. CONCLUSION: These syndromes have aggravated each other, and possibly the explanation for the cephalalgia remission was the control of AIHA and SLE. It features a rare case in literature and thus warrants discussion.

INTRODUÇÃO: Hemicrania contínua é uma forma rara de cefaléia caracterizada por cefaleia crônica e persistente em apenas um lado da cabeça. OBJETIVOS: Neste relato apresentamos o caso de um paciente com hemicrania contínua e lúpus eritematoso sistêmico (LES). MÉTODOS: Coletamos dados dos pacientes por meio do prontuário eletrônico. Posteriormente, revisamos a literatura sobre a hemicrania contínua e sua fisiopatologia e correlação com alterações neurovasculares, inflamação e LES. RESULTADOS: Uma mulher de 42 anos recorreu ao serviço de urgência devido ao agravamento da cefaleia unilateral constante, presente nos últimos 6 meses. O paciente relatou cefaleia de alta intensidade (10/10) em toda a hemicrânia esquerda com irradiação para o ombro esquerdo. Ao exame físico apresentava nistagmo, vertigem e cefaléia agravada associada à movimentação corporal e, apesar de não apresentar espessamento do nervo óptico. Além disso, ela apresentava icterícia, taquicardia e esplenomegalia. Os exames complementares evidenciaram anemia profunda, depleção do sistema complemento e fatores antinucleares, sugerindo uma possível anemia hemolítica (AIHA) por LES. Iniciou-se tratamento com hidrocortisona e prednisona, associadas a amitriptilina, fluoxetina e diazepam, atingindo remissão completa. CONCLUSÃO: Essas síndromes agravaram-se mutuamente e possivelmente a explicação para a remissão da cefaléia foi o controle da AIHA e do LES. Apresenta um caso raro na literatura e, portanto, merece discussão.

Atención odontológica intrahospitalaria en el Hospital de Especialidades Carlos Andrade Marín / Intrahospital Dental Care at Carlos Andrade Marín Specialties Hospital

La Odontología Intrahospitalaria requiere un modelo de atención conformado por un conjunto de profesionales que contribuyan de manera coordinada y simbiótica, para devolver o mantener la salud bucodental del paciente, siendo el hospital es un ambiente acertado para alcanzar este objetivo, ya que permite realizar un tratamiento de manera coordinada y transdisciplinaria. Los pacientes con enfermedades sistémicas o crónicas, síndromes o discapacidades, requieren de un abordaje integral, en donde exista un trabajo en conjunto, entre las especialidades médico-quirúrgicas y odontológicas, teniendo siempre un apoyo en la historia clínica del paciente o en las interconsultas realizadas de manera apropiada. La implementación de la valoración odontológica en pacientes hospitalizados previa a una intervención quirúrgica, radioterapia, quimioterapia, trasplantes, entre otros, ha sido demostrado que producen una mejoría en la calidad de vida del paciente mientras cursa su enfermedad, favoreciendo también en el costo que representa al sistema de salud una complicación durante el trata-miento de su enfermedad de base.

In-hospital Dentistry requires a care model made up of a group of professionals who contribute in a coordinated and symbiotic manner, to restore or maintain the patient's oral health, with the hospital being a suitable environment to achieve this objective, since it allows for treatment. in a coordinated and transdiscipli-nary manner.Patients with systemic or chronic diseases, syndromes or disa-bilities require a comprehensive approach, where there is joint work between the medical-surgical and dental specialties, always having support in the patient's clinical history or in the interconsultations carried out appropriately.The implementation of dental assessment in hospitalized pa-tients prior to surgery, radiotherapy, chemotherapy, transplants, among others, has been shown to produce an improvement in the patient's quality of life while their illness is ongoing, also fa-voring the cost it represents. to the health system a complication during the treatment of their underlying disease.

Calidad de vida en pacientes con enfermedad de Pompe: estudio observacional / Quality of Life in Patients with Pompe Disease: Cross-Sectional Study

Introducción: La enfermedad de Pompe es una enfermedad genética multisistémica y rápidamente progresiva, que causa compromiso muscular (esquelético, cardíaco y liso), severa hipotonía y dificultad en la deglución. Debido a la naturaleza de la enfermedad, la calidad de vida de las personas que la padecen puede verse más afectada con respecto a la población general. Método: Se llevó a cabo un estudio descriptivo de corte transversal. Se diseñó un instrumento tipo encuesta con preguntas de caracterización sociodemográfica y referentes a la enfermedad. Para medir la calidad de vida se aplicó el Medical Outcomes Study 36-Item Short Form (SF-36) Questionnaire. Se hizo una comparación entre grupos, con nivel de significancia de 0,05. Resultados: Se obtuvieron encuestas de 27 pacientes de seis países. La edad media fue de 40,52 años, el 59 % fueron mujeres, el 51 % casados, el 63 % activos laboralmente, con edad media de diagnóstico de 30,3 años (SD = 15,557). La dimensión con menor media fue el rol físico (10,2; IC 95 % = 1,5-21,9), mientras que la de mayor media fue la salud mental (65,5; IC 95 % = 56,9-74,0). El 29,7 % (IC 95 % = 11,2-48,0) de los encuestados consideró sentirse en peores condiciones de salud que el año anterior. Discusión: Se evidencia una baja calidad de vida en pacientes con EP, en comparación con la población general, si se tienen en cuenta otros estudios que utilizan el mismo cuestionario. Conclusiones: Se evidencia una baja calidad de vida en los pacientes con enfermedad de Pompe participantes; las dimensiones asociadas con parámetros físicos fueron las de menores puntuaciones.

Introduction: Pompe disease is a rapidly progressive, multisystemic genetic disease that causes muscle involvement (skeletal, cardiac and smooth), severe hypotonia and difficulty in swallowing. Due to the nature of the disease, the quality of life may be more affected compared to the general population. Method: A descriptive cross-sectional study was carried out. A survey-type instrument was designed with questions of sociodemographic characterization and those referring to the disease. To measure Quality of Life, the Medical Outcomes Study 36-Item Short Form (SF-36) questionnaire was applied. A comparison was made between groups with a significance level of 0,05. Results: 27 surveys of patients from six countries were obtained. The mean age 40.52 years, women 59 %, married 51 %, 63 % active in employment, with a mean age of diagnosis of 30.3 years (SD = 15,557). The dimension with the lowest mean was the Physical Role (10.2; 95 % CI = 1.5 - 21.9), while the one with the highest mean was the Mental Health dimension (65.5; 95 % CI = 56.9 - 74.0). 29.7 % (95 % CI = 11.2 - 48.0) of those surveyed considered they felt in worse health conditions than the previous year. Discussion: Low quality of life is evidenced in patients with PD in comparison to the general population described in other studies using the same questionnaire. Conclusions: A low quality of life is evidenced in the study individuals where the dimensions related to the physical area were lower.

Estratégias de Avaliação de Tecnologias em Saúde (ATS) para medicamentos para doenças raras: uma revisão rápida de escopo / Health Technology Assessment (HTA) strategies for drugs in rare diseases: a rapid scope review

A Avaliação de Tecnologias em Saúde (ATS) considera os domínios de benefícios clínicos, perfil epidemiológico, inovação, custo-efetividade, ética e de equidade no processo de decisão dos gestores em saúde. No contexto dos medicamentos para doenças raras, é desafiador o trabalho da ATS, dada a baixa disponibilidade de evidências robustas e o alto custo unitário das tecnologias. O objetivo da revisão foi analisar as estratégias disponíveis de avaliação das demandas de incorporação de medicamentos para o tratamento de doenças raras em sistemas de saúde. Foi realizada uma revisão rápida com busca estruturada na base de dados MEDLINE (via PubMed), Cochrane Library e Health Systems Evidence. Incluíram-se estudos sobre estratégias de avaliação de medicamentos utilizados para tratamento de doenças raras. Adicionalmente, foram realizadas buscas nas Agências de ATS do Brasil, Austrália, Nova Zelândia, Canadá, Reino Unido, França, Estados Unidos e Alemanha. A síntese dos resultados foi qualitativa com o agrupamento dos achados nos seguintes eixos temáticos: Segurança e efetividade, Custo-efetividade, Impacto orçamentário e Perspectiva da sociedade. Foram identificadas 267 publicações, sendo selecionadas 16 das bases de dados indexadas e 7 da literatura cinzenta. Com a análise dos documentos, pode-se concluir que a adoção de critérios específicos harmonizada com o atual modelo de ATS é um possível caminho a ser seguido no contexto dos medicamentos para doenças raras. Concomitante a isso, abordagens no sentido de incentivo a pesquisa e produção de dados de mundo real e a criação de comitês específicos para tratativa do tema nas agências de ATS apresentam-se como alternativa para lidar com as fragilidades no contexto de doenças raras.

The Health Technology Assessment (HTA) considers evidence regarding clinical benefits, epidemiological profile, innovation, cost-effectiveness, ethics and equity in its assessment process to support managers' decisions. In the context of drugs in rare diseases, the work of the ATS is challenging given the low availability of evidence and the high cost of technologies. The objective of the review was to analyze the available strategies for evaluating the demands for incorporating drugs for the treatment of rare diseases in health systems. A rapid review was performed with a structured search in the MEDLINE database (via PubMed), the Cochrane Library and Health Systems Evidence. Studies on strategies for evaluating drugs used to treat rare diseases were included and, additionally, searches were carried out in ATS Agencies in Brazil, Australia, New Zealand, Canada, United Kingdom, France, United States and Germany. The synthesis of the results was qualitative, grouping the major ones into thematic axes: Safety and effectiveness, Cost-effectiveness, Budgetary impact and Society's perspective. 267 publications were identified, 16 selected from indexed databases and 7 from gray literature. With the analysis of the documents, it can be concluded that the adoption of specific criteria harmonized with the current ATS model is a possible path to be followed in the context of drugs for rare diseases. At the same time, approaches to encourage research and the creation of specific committees to deal with the issue in HTA agencies would complement actions towards the consolidation of this work.

Innovative mechanisms of pre-marketing authorization access for rare diseases in Brazil: a case study of pabinafusp-alfa for mucopolysaccharidosis type II / Mecanismos inovadores de acesso pré-comercialização a tecnologias para doenças raras no Brasil: um estudo de caso de alfapabinafuspe para mucopolissacaridose tipo II

Patients with rare diseases frequently face unmet medical needs due to the high costs, lengthy development times, and slow approval processes for new treatments. This case study discusses innovative access alternatives for rare diseases in Brazil, focusing on early access to pabinafusp-alfa for mucopolysaccharidosis type II (MPS-II), a rare genetic lysosomal storage disease characterized by a deficiency of the enzyme iduronate-2-sulfatase. From September 2018 to March 2023, 20 Brazilian MPS-II patients received pabinafusp-alfa through a clinical research protocol. This enzyme replacement therapy (ERT) crosses the blood-brain barrier to address central nervous system manifestations unmet by existing treatments. Patients' participation in the clinical study resulted in an estimated BRL 65 million in cost savings for the public healthcare system compared to conventional ERT with idursulfase-alfa and potentially better clinical outcomes. The case study underscores the importance of innovative mechanisms in addressing patients' medical needs. Early access alternatives include: a) clinical study access, with execution/development aligned with healthcare managers and linked to future access strategies; b) regulatory-level risk-sharing, considering effectiveness uncertainties and the possibility of market withdrawal and/or reimbursement in case of negative results; and c) drug pre-delivery, with payment contingent on positive phase III clinical study outcomes. Although public-private partnerships in clinical research are underused, they could benefit all stakeholders by accelerating drug development, facilitating early patient access to innovative medicines, and generating healthcare system savings, particularly for rare diseases.

Pacientes com doenças raras frequentemente enfrentam necessidades médicas não atendidas devido aos altos custos, longos tempos de desenvolvimento e processos de aprovação lentos para novos tratamentos. Este estudo de caso discute alternativas inovadoras de acesso para doenças raras no Brasil, com foco no acesso precoce ao alfapabinafuspe para mucopolissacaridose tipo II (MPS-II), uma doença lisossômica de armazenamento genético rara, caracterizada por uma deficiência da enzima iduronato-2-sulfatase. De setembro de 2018 a março de 2023, 20 pacientes brasileiros com MPS-II receberam alfapabinafuspe por meio de pesquisa clínica. Essa terapia de reposição enzimática (TRE) atravessa a barreira hematoencefálica para tratar manifestações do sistema nervoso central não atendidas pelos tratamentos existentes. A participação dos pacientes no estudo clínico resultou em uma economia estimada de 65 milhões de reais para o sistema público de saúde, em comparação com a TRE convencional com idursulfase alfa, além de potencialmente melhores resultados clínicos. O estudo de caso destaca a importância de mecanismos inovadores no atendimento das necessidades médicas dos pacientes. As alternativas de acesso precoce incluem: a) acesso por meio de estudos clínicos, com execução/desenvolvimento alinhada aos gestores de saúde e vinculada a estratégias futuras de acesso; b) compartilhamento de risco em nível regulatório, considerando as incertezas de eficácia e a possibilidade de retirada do mercado e reembolso em caso de resultados negativos; e c) pré-entrega do medicamento, com pagamento condicionado aos resultados positivos do estudo clínico de fase III. Embora as parcerias público-privadas em pesquisa clínica sejam subutilizadas, elas poderiam beneficiar todas as partes interessadas ao acelerar o desenvolvimento de medicamentos, facilitar o acesso precoce dos pacientes a medicamentos inovadores e gerar economias para o sistema de saúde, especialmente para doenças raras.

Aspectos clínicos e diagnósticos, qualidade de vida, utilidade, adesão terapêutica e custos para angioedema hereditário associado à deficiência de C1-esterase / Clinical and diagnostic aspects, quality of life, usefulness, therapeutic adherence and costs for hereditary angioedema associated with C1-esterase deficiency

Introdução: O angioedema hereditário associado à deficiência de C1 esterase (AEH-C1-INH) é uma doença rara (DR) que se manifesta com a ocorrência de episódios recorrentes de angioedema não pruriginoso subcutâneo ou submucoso, o que gera impactos em todos os aspectos da vida dos indivíduos. Objetivo: Avaliar a qualidade de vida e a jornada clínica e assistencial dos pacientes com AEH-C1-INH. Material e Métodos: Trata-se de um estudo observacional ambispectivo em que foram aplicados questionários relacionados à qualidade de vida e jornada assistencial, além da coleta de dados clínicos dos prontuários nos tempos 0, 6 e 12 meses. Resultados: Foram recrutados 15 indivíduos com AEH-C1-INH e a mediana (I.I.Q) de idade da amostra foi de 38 anos (30-43). O tempo médio entre os primeiros sintomas e o diagnóstico foi de 8 anos. Os dados clínicos demonstraram história familiar positiva expressiva, ocorrência importante de edema de laringe em algum momento da vida e altos índices de recorrência das crises de angioedema durante os 12 meses de estudo. A qualidade de vida apresentou prejuízo importante principalmente em aspectos físicos, emocionais e vitalidade, sem variações significativas no tempo de estudo. Além disso, vale destacar a perda de produtividade expressiva associada a gastos médios de R$3.017,00 para medicamentos e R$598,00 para exames complementares em 12 meses. Conclusão: Observa-se um panorama de perda significativa de qualidade de vida relacionada ao AEH-C1-INH, principalmente por impactos da saúde física e emocional no exercício das atividades rotineiras. Ressaltam-se os impactos econômicos da jornada terapêutica, tanto pela perda de produtividade quanto pela necessidade de financiar medicamentos e exames que deveriam ser responsabilidade do Estado por meio do Sistema Único de Saúde (SUS). Portanto, fica clara a importância de medidas públicas que busquem amenizar os impactos causados pela doença nos indivíduos acometidos.

Introduction: Hereditary Angioedema associated with C1 esterase deficiency (HAE-C1-INH) is a rare disease (RD) that manifests with recurrent episodes of non-pruritic subcutaneous or submucosal angioedema, which impacts on all aspects of the individual's life. Objective: To evaluate the quality of life and the clinical and care journey of patients with HAE-C1-INH. Material and Methods: This is an ambispective observational study in which questionnaires related to quality of life and care journey were applied, in addition to the clinical data collection from medical records at 0, 6 and 12 months. Results: 15 subjects with HAE-C1-INH were recruited and the median (IQR) age of the sample was 38 years (30-43). The average time between the first symptoms and diagnosis was 8 years. The clinical data showed a substantial positive family history, considerable occurrence of laryngeal edema at some point in life and high rates of recurring angioedema crises during the 12 months of the study. Quality of life was significantly impaired, especially in terms of physical and emotional aspects and vitality, with no significant variations over the study period. It is also worth noting the major loss of productivity associated with average costs of R$3,017.00 for medication and R$598.00 for complementary tests over 12 months. Conclusion: There is a noticeable loss of quality of life related to HAE-C1-INH, mainly due to the impact on physical and emotional health when carrying out routine activities. The economic impacts of the therapeutic journey stand out, both due to the loss of productivity and the need to finance medicines and tests that should be the responsibility of the State through the Unified Health System (SUS). Therefore, the importance of public measures that seek to mitigate the impacts caused by the disease on affected individuals is evident.

Hemophagocytic syndrome in a patient with Fanconi anemia and VACTERL association / Síndrome hemofagocítica em paciente com anemia de Fanconi e associação VACTERL

INTRODUCTION: Hemophagocytic syndrome results from hyperactivity of histiocytes and lymphocytes, triggered by infections, mainly viral by cytomegalovirus, Epstein-Barr and herpes. Fanconi anemia (FA) is a rare genetic disease with heterogeneous symptoms common to other diseases such as VACTERL, a disease of unknown etiology in which there are several congenital malformations. The concomitance of Fanconi and VACTERL anemia occurs in 5 to 30% of FA patients. REPORT: A 14-month-old male infant was admitted to investigate fever, hepatosplenomegaly, and granulopenia. The patient was diagnosed with hemophagocytic syndrome due to hyperferritinemia, bone marrow hemophagocytosis, transaminase elevation, decreased fibrinogen, and cytomegalovirus (CMV) infection confirmed by serology and PCR. The test with mitomycin C (MMC) showed chromosomal fragility. The patient was diagnosed with a VACTERL/FA association for having a clinic and a test compatible with both FA and VACTERL. CONCLUSION: The VACTERL/FA association is seldom described, but is present in pediatric medical practice. This study presented the main clinical-laboratory aspects and reviewed the main aspects of the concurrence of this pathology.

INTRODUÇÃO: A síndrome hemofagocítica decorre da hiperatividade de histiócitos e linfócitos e é desencadeada por infeções, principalmente virais por citomegalovírus, Epstein-barr e herpes. A anemia de Fanconi (AF) é uma doença genética rara com sintomas heterogêneos em comum a outras doenças como a associação VACTERL, uma doença de etiologia desconhecida na qual existe diversas mal formações congênitas. A concomitância da anemia de Fanconi e VACTERL é descrita em 5 a 30% dos pacientes AF. RELATO: Lactente de 14 meses, sexo masculino, admitido para investigar um quadro de febre, hepatoesplenomegalia e granulopenia. Os exames laboratoriais mostraram a hiperferritemia, elevação da transaminases, medula óssea com hemofagocitose e, sorologia e PCR positivos para citomegalovírus (CMV). O paciente foi diagnosticado com síndrome hemofagocítica por citomegalovírus. Como havia também hipoplasia do polegar esquerdo, presença de hemivértebra, agenesia renal e teste positivo de fragilidades cromossômicas com mitomicina C (MMC), o paciente foi diagnosticado com associação VACTERL/AF. CONCLUSÃO: O citomegalovírus quando infecta pacientes com problemas de imunidade como AF, apresenta risco de desencadear a síndrome hemofagocítica. A associação VACTERL/AF é pouco descrita, mas presente na prática médica da pediatria. Esse estudo descreveu os principais aspectos clínicos-laboratoriais e revisou os aspectos fundamenais descritos sobre a concomitância dessas patologias.

A Chinese interpretation for the "ACGS Best Practice Guidelines for Variant Classification in Rare Disease 2020" / 中华医学遗传学杂志

ACGS Best Practice Guidelines for Variant Classification in Rare Disease 2020, a supplementary practical guidelines, is based on the Standards and Guidelines for the Interpretation of Sequence Variations issued by the American Society for Medical Genetics and Genomics (ACMG) and the Association of Molecular Pathology (AMP) in 2015 by the British Medical Genetics Society under the Clinical Genomics Society (ACGS), and has integrated the detailed rules of standards developed by the ClinGen Sequence Variant Interpretation (SVI) Working Group by 2020. The further development of the ACMG/AMP guidelines is currently undertaken by the ClinGen SVI working group in the United States, which focuses on the classification of high penetrance and protein coding variants. ClinGen has established many expert panels on variants for specific diseases which required various evidence thresholds and is currently developing disease/gene specific guidelines. The British Medical Genetics Society has collected and integrated information on the guidelines for sequence variation classification and their extended rules, forming its own "2020 ACGS Best Practice Guidelines for Rare Disease Variation Classification" and is regularly updating it. The author has translated and summarized it for the reference of Chinese Medical Genetics Practitioners.

Helsmoortel-Van der Aa syndrome due to hotspot mutation of ADNP gene and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To summarize the clinical features and biological characteristics of Helsmoortel Van der Aa syndrome (HVDAS) due to hotspot mutations of the ADNP gene in order to facilitate early diagnosis.@*METHODS@#Clinical data and result of genetic testing for a girl with HVDAS due to hotspot mutation of the ADNP gene was summarized. Related literature was also reviewed.@*RESULTS@#The patient, a 2-year-old girl, had presented with growth retardation, facial dysmorphism, psychomotor and language delay and recurrent respiratory infections. Whole exome sequencing revealed that she has harbored a heterozygous c.2496_2499delTAAA (p.Asn832Lysfs*81) variant of the ADNP gene, which was not found in either of her parents.@*CONCLUSION@#Although the typical features of the HVDAS have included intellectual disability and autism spectrum disorders, growth retardation and premature primary tooth eruption may also be present. In addition, the phenotypic difference among individuals carrying hot spot variants of the ADNP gene was not prominent.

Glycosylphosphatidylinositol biosynthesis deficiency 15 caused by GPAA1 gene mutation: a rare disease study / 中国当代儿科杂志

A boy, aged 6 years, attended the hospital due to global developmental delay for 6 years and recurrent fever and convulsions for 5 years. The boy was found to have delayed mental and motor development at the age of 3 months and experienced recurrent fever and convulsions since the age of 1 year, with intermittent canker sores and purulent tonsillitis. During the fever period, blood tests showed elevated white blood cell count, C-reactive protein, and erythrocyte sedimentation rate, which returned to normal after the fever subsides. Electroencephalography showed epilepsy, and genetic testing showed compound heterozygous mutations in the GPAA1 gene. The boy was finally diagnosed with glycosylphosphatidylinositol biosynthesis deficiency 15 (GPIBD15) and periodic fever. The patient did not respond well to antiepileptic treatment, but showed successful fever control with glucocorticoid therapy. This article reports the first case of GPIBD15 caused by GPAA1 gene mutation in China and summarizes the genetic features, clinical features, diagnosis, and treatment of this disease, which provides a reference for the early diagnosis and treatment of GPIBD15.

Clinical diagnostic techniques for rare genetic diseases in children: current status, advances, and thoughts / 中国当代儿科杂志

Rare diseases refer to a group of single diseases with low incidence rates, complex pathogeneses, severe disease conditions, and rapid progression. Most rare diseases have a genetic background and may occur in childhood. Paying attention to the rare genetic diseases in children and performing early diagnosis and treatment can effectively delay the course of disease and improve the quality of life of children. Many rare diseases can be diagnosed with the help of various experimental techniques, but the diagnosis of rare diseases is still not widely understood. This article summarizes the laboratory diagnostic techniques currently used for rare genetic diseases in children, so as to provide clues for the diagnosis and treatment of such diseases and help to enhance the theoretical understanding and precise medical treatment of rare genetic diseases in children.